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ANESTHETIC PHARMACOLOGY

Lidocaine Increases Intracellular Sodium Concentration Through a Na⁺-H⁺ Exchanger in an Identified Lymnaea Neuron

From the Department of Anesthesiology and Intensive Care, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki, Japan.

Address correspondence and reprint requests to Dr. Onizuka, Department of Anesthesiology and Intensive Care, Faculty of Medicine, University of Miyazaki, Kiyotake-Cho, Miyazaki 889-1692, Japan. Address e-mail to pirotann{at}med.miyazaki-u.ac.jp.

BACKGROUND: The intracellular sodium concentration ([Na⁺]in) is related to neuron excitability. For [Na⁺]in, a Na⁺-H⁺ exchanger plays an important role, which is affected by intracellular pH ([pH]in). However, the effect of lidocaine on [pH]in and a Na⁺-H⁺ exchanger is unclear. We used neuron from Lymnaea stagnalis to determine how lidocaine affects [pH]in, Na⁺-H⁺ exchanger, and [Na⁺]in.

METHODS: Intracellular sodium imaging by sodium-binding benzofuran isophthalate and intracellular pH imaging by 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein were used to measure [Na⁺]in and [pH]in. Measurements for [Na⁺]in were made in normal, Na⁺ free saline, with modified extracellular pH, and a Na⁺-H⁺ exchanger antagonist [(5-N-ethyl-N-isopropyl amiloride, N-methylisopropylamiloride, and 5-(N,N-hexamethylene)-amiloride) pretreatment trials. Furthermore, [Na⁺]in and [pH]in were recorded simultaneously. From 0.1 to 10 mM, lidocaine, mepivacaine, bupivacaine, prilocaine, and QX-314 were evaluated.

RESULTS: Lidocaine, mepivacaine, and prilocaine increased the [Na⁺]in in a dose-dependent manner. In contrast, QX-314 did not change the [Na⁺]in at each dose. In the Na⁺ free saline or in the presence of each Na⁺-H⁺ exchanger antagonist, lidocaine failed to increase [Na⁺]in. Lidocaine, mepivacaine, and prilocaine induced a significant decrease in [pH]in below baseline with an increase in [Na⁺]in. In contrast, QX-314 did not change the [pH]in. These results demonstrated that lidocaine increases [Na⁺]in through Na⁺-H⁺ exchanger activated by intracellular acidification, which is induced by the proton trapping of lidocaine. This [Na⁺]in increase and [pH]in change induces cell toxicity.

CONCLUSION: Lidocaine increases the [Na⁺] through a Na⁺-H⁺ exchanger by proton trapping.

Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999